A meta-analytic evaluation of the effectiveness and durability of psychotherapy for adults presenting with functional dissociative seizures.

BACKGROUND: Psychological interventions are the most recommended treatment for functional/dissociative seizures (FDS); however, there is ongoing uncertainty about their effectiveness on seizure outcomes. METHODS: This systematic review and meta-analysis synthesises the available data. In February 2023, we completed a systematic search of four electronic databases. We described the range of seizure-related outcomes captured, used meta-analytic methods to analyse data collected during treatment and follow-up; and explored sources of heterogeneity between outcomes. RESULTS: Overall, 44 relevant studies were identified involving 1,300 patients. Most were categorised as being at high (39.5 %) or medium (41.9 %) risk of bias. Seizure frequency was examined in all but one study; seizure intensity, severity or bothersomeness in ten; and seizure duration and cluster in one study each. Meta-analyses could be performed on seizure freedom and seizure reduction. A pooled estimate for seizure freedom at the end of treatment was 40 %, while for follow-up it was 36 %. Pooled rates for ≥50 % improvement in seizure frequency were 66 % and 75 %. None of the included moderator variables for seizure freedom were significant. At the group level, seizure frequency improved during the treatment phase with a moderate pooled effect size (d = 0.53). FDS frequency reduced by a median of 6.5 seizures per month. There was also evidence of improvement of the other (non-frequency) seizure-related measures with psychological therapy, but data were insufficient for meta-analysis. CONCLUSIONS: The findings of this study complement a previous meta-analysis describing psychological treatment-associated improvements in non-seizure-related outcomes. Further research on the most appropriate FDS-severity measure is needed.

A systematic review of psychological interventions in adults with pulmonary hypertension: Is the evidence-base disproportionate to the problem?

INTRODUCTION: Our understanding of the psychological impact of living with pulmonary hypertension (PH) is growing, particularly for how anxiety and depression present in this group. There is evidence for the use of psychological interventions in other chronic lung conditions; however, trials focusing on adults with PH have yet to be subject to a systematic review. METHODS: We systematically searched four databases for evidence examining the effectiveness of psychological interventions for adults with PH. A narrative approach has been used to present findings. RESULTS: Overall, 186 unique articles were identified of which four were suitable. Data was gathered from 143 individuals. Cognitive behavioural therapy (CBT), metacognitive therapy (MCT) or counselling were investigated. All three studies reported a significant reduction in anxiety and depression, and some secondary outcomes were also associated with change. DISCUSSION: The evidence supporting the use of psychological therapies for adults with PH is promising, although limited. There is an urgent need for more research in this area to better understand how we can support this clinical group.

A meta-analytic review of the effectiveness of psychological treatment of functional/dissociative seizures on non-seizure outcomes in adults.

Psychological therapies are considered the treatment of choice for functional/dissociative seizures (FDSs). Although most previous studies have focused on seizure persistence or frequency, it has been argued that well-being or health-related quality of life outcomes may actually be more meaningful. This study contributes by summarizing and meta-analyzing non-seizure outcomes to quantify the effectiveness of psychological treatment in this patient group. A pre-registered systematic search identified treatment studies (e.g., cohort studies, controlled trials) in FDSs. Data from these studies were synthesized using multi-variate random-effects meta-analysis. Moderators of treatment effect were examined using treatment characteristics, sample characteristics, and risk of bias. A total of 171 non-seizure outcomes across 32 studies with a pooled sample size of N = 898 yielded a pooled effect-size of d = .51 (moderate effect size). The outcome domain assessed and the type of psychological treatment were significant moderators of reported outcomes. Greater rates of improvement were demonstrated for outcomes assessing general functioning. Behavioral treatments emerged as particularly effective interventions. Psychological interventions are associated with clinical improvements across a broad array of non-seizure outcomes, over and above seizure frequency, in adults with FDSs.

Can self-compassion help us better understand the impact of pulmonary hypertension on those with the condition and their carers? A cross-sectional analysis.

Pulmonary hypertension (PH) can have a multifaced impact both on the affected individual and close family members. However there are relatively few studies that have sought to identify potential protective factors. Individual differences in ability to be self-compassionate are known to be implicated in adjustment in other long-term conditions and are now featuring in the provision of care for a number of conditions. This is a cross-sectional study that investigated the relationship between self-compassion, demographic, PH-related information, and measures of psychosocial functioning in adults with PH (n = 65) and caregivers (n = 29). Individuals with PH and caregivers of someone with PH completed self-report measures on demographic and clinical factors, anxiety, depression, self-compassion, and in those with PH, health-related quality of life, and in carers, caregiver burden. Data were analyzed using hierarchical regression analyses. Surprisingly, participants with PH and caregivers did not significantly differ on rates of depression (p = 0.19) or anxiety (p = 0.57) with both scoring relatively high. Components of self-compassion were associated with psychological functioning in both individuals and caregivers. Greater self-compassion was associated with fewer symptoms of anxiety and depression, and greater health-related quality of life in individuals with PH and lower burden in caregivers. More specifically, multiple regression analyses revealed after controlling for age, gender, and duration of PH, self-compassion was a significant predictor of anxiety and depression in people with PH, and of anxiety and caregiver burden in carers. These findings add to the evidence base indicating that there can be a range of burdens experienced by both people living with PH and their wider families. Further, this study uniquely suggests that psychological and supportive interventions that seek to build self-compassion may be useful to develop and test in this clinical group.

Imagery re-scripting for PTSD: session content and its relation to symptom improvement.

Imagery rescripting (ImRs) is a therapy technique that, unlike traditional re-living techniques, focuses less on exposure and verbal challenging of cognitions and instead encourages patients to directly transform the intrusive imagery to change the depicted course of events in a more desired direction. However, a comprehensive account of how and in what circumstances ImRs brings about therapeutic change is required if treatment is to be optimised, and this is yet to be developed. The present study reports on the development of a coding scheme of ImRs psychotherapy elements identified in the literature as potential ImRs mechanisms. The codes were assessed in relation to short-term outcomes of 27 individuals undergoing ImRs for post-traumatic stress disorder. The timing of the change in the image, degree of activation of the new image and associated cognitive, emotional and physiological processes, self-guided rescripting, rescript believability, narrative coherence and cognitive and emotional shift were identified as being related to symptom change and so are potentially important factors for the re-scripting process.

Serum concentration of taurochenodeoxycholic acid predicts clinically significant portal hypertension.

BACKGROUND & AIMS: Severity of portal hypertension is usually quantified by measuring the hepatic venous pressure gradient (HVPG). However, due to its invasiveness, alternative markers are being sought. Bile acids (BA), being synthesized, metabolized, and transported by the liver, seem to have the potential to serve as endogenous markers. The aim of the present study was to determine whether serum BA reflect the severity of portal hypertension. METHODS: We correlated serum concentrations of individual BA with portal pressure (as HVPG) in an exploratory cohort of 21 cirrhotic patients with portal hypertension. The predictive potential of selected candidates was then confirmed in an independent validation cohort (n = 214). Additionally, nine previously published noninvasive markers were added to the stepwise logistic regression model to identify the most relevant ones, which were eventually used to create a prognostic index of portal hypertension. RESULTS: Serum levels of taurochenodeoxycholic acid (TCDCA) significantly correlated with HVPG and showed a high potential to predict clinically significant portal hypertension (HVPG ≥ 10 mm Hg: AUROC = 0.97 ± 0.06). This was confirmed in the validation cohort (AUROC = 0.96 ± 0.01). The predictive index (constructed based on AST/ALT, spleen diameter, and TCDCA concentration) was able to distinguish clinically significant portal hypertension with 95% sensitivity and 76% specificity. CONCLUSIONS: TCDCA seems to be a promising noninvasive marker of clinically significant portal hypertension. Its predictive potential may be further enhanced when it is combined with both the AST/ALT ratio and spleen diameter.

Cognitive and behavioral processes predict anxiety and depression in patients with pulmonary hypertension.

Emotional and psychological difficulties cannot fully be explained by disease-related factors in people with pulmonary hypertension (PH). This study examined the relationship between anxiety, depression, demographic, objective and subjective PH factors, and self-reported cognitive and behavioral processes, which have been associated with mood in clinical and nonclinical samples. This is a secondary analysis of baseline data from 77 adults with PH who took part in a randomized controlled trial of a self-help intervention targeting anxiety in PH. Participants completed self-report measures including: demographic (age, gender, ethnicity, education, employment) and clinical questionnaire (PH diagnosis, functional class, years since diagnosis), depression (PHQ-9), anxiety (GAD-7), health-related quality of life (emPHAsis-10), dyspnea (D12), and cognitive and behavioral processes (CBP-Q) scale. Data were analyzed using correlational and regression analyses. Overall, 70% and 63% of participants scored above the clinical cut off for anxiety and depression, respectively. Demographics were not associated with anxiety or depression. PH-related factors were correlated with depression but not anxiety. A multiple regression analysis suggested dyspnea and cognitive processes significantly predicted anxiety whereas behavioral processes were not a unique predictor. In contrast, dyspnea and behavioral processes predicted depression whereas cognitive processes did not. While a body of evidence exists demonstrating people with PH are more likely to experience anxiety and depression, less is known about factors that cause and maintain these disorders. Findings highlight the significance of subjective factors that could be a target for screening and psychological treatments for emotional difficulties, such as cognitive behavioral therapy.

Coping styles associated with depression, health anxiety and health-related quality of life in pulmonary hypertension: cross-sectional analysis.

OBJECTIVES: Pulmonary hypertension (PH) is a life-shortening disease associated with early mortality and high morbidity. With advancements in medical treatment, people are living longer with the disease, and research is now needed to explore variables that help to enhance patient-reported outcomes. This study investigated the coping strategies of individuals with PH and examined the relationship between coping, depression, health anxiety and health-related quality of life (HRQoL). DESIGN: A cross-sectional survey design was used. PARTICIPANTS: Participants (n=121) were recruited from membership of Pulmonary Hypertension Association (PHA) UK. OUTCOME MEASURES: Participants completed a series of questionnaires assessing depression (Patient Health Questionnaire-9), health anxiety (Short Health Anxiety Inventory), HRQoL (emPHasis-10) and coping (Brief COPE). A principal component analysis was used to identify participants' coping profile. A series of correlational, linear and moderated multiple regression analyses were performed to examine the relationship between coping and health-related outcomes. RESULTS: Overall, 43% participants met criteria for potential clinical depression. Depression and health anxiety were strongly associated with HRQoL, explaining 37% and 30% of variance respectively (p<0.001). A principal component analysis identified a four-component model of coping. Dimensions were named based on construct items: 'cognitive and affirmation coping' (seven items), 'passive coping' (four items), 'external coping' (seven items) and 'substance use coping' (two items). Cognitive and affirmation and external coping moderated the relationship between depression and HRQoL, with high use of these coping strategies reducing the impact of depression on HRQoL. External coping also moderated the effect of health anxiety on HRQoL. CONCLUSIONS: The results uniquely highlight the importance of coping styles and psychological distress in predicting HRQoL in PH. Our findings indicate the importance to assess for psychological distress in this population and suggest the need to offer psychological interventions that take into account coping resources and strategies.

Metabolic dysfunction-associated fatty liver disease (MAFLD) as a more accurate name for NAFLD - common aspects of pathogenesis.

Non-alcoholic fatty liver disease is considered a common hepatic manifestation of metabolic syndrome. With respect to the pathogenesis of liver steatosis and non-alcoholic steatohepatitis, recently a consensus of international experts proposed a change in the name of the disease to metabolic dysfunction-associated fatty liver disease (MAFLD). The new name should not only better reflect the pathogenesis, but also better stratify risks of the patients treatment and eliminate stigmatization originating from the presence of the term "alcohol" in the name of the disease. This work also emphasizes the common pathophysiological mechanisms involved in both metabolic syndrome and liver steatosis, such as dyslipidemia, insulin resistance, gut dysbiosis, oxidative stress, genetic, epigenetic and hormonal factors.

What do we know about non-epileptic seizures in adults with intellectual disability: A narrative review.

Psychogenic non-epileptic seizures (PNES) superficially resemble epileptic seizures, but are not associated with abnormal electrical activity in the brain. PNES are a heterogeneous entity and while there is increasing interest in the characterisation of PNES sub-groups, little is known about individuals with PNES who have an intellectual disability (ID). ID is a lifelong condition characterised by significant limitations in cognitive, social and practical skills. ID (commonly with comorbid epilepsy) has been identified as a risk factor for developing PNES. However, people with ID are often excluded from research in PNES. This has unfortunately resulted in a lack of evidence to help inform practice and policy for this population. This narrative review synthesises the currently available evidence in terms of the epidemiology, demographic and clinical profile of adults with PNES and ID. There is a particular focus on demographics, aetiological factors, PNES characteristics, diagnosis and treatment of the condition in this population. Throughout this article, we critique the existing evidence, discuss implications for clinical practice and highlight the need for further research and enquiry. What emerges from the evidence is that, even within the sub-group of those with ID, PNES are a heterogeneous condition. Individuals with ID and PNES are likely to present with diverse and complex needs requiring multidisciplinary care. This review is aimed at the broad range of healthcare professionals who may encounter this group. We hope that it will stimulate further discussion and research initiatives.

Serum markers in diagnostics of steatohepatitis.

Along with the increasing incidence and prevalence of obesity and the metabolic syndrome, the number of patients with its hepatic manifestation - NAFL, characterized by triglyceride storage in liver, is rising. NAFL (non-alcoholic fatty liver) is now, with the prevalence of 40 %, the most common liver disease in Western countries. Despite that NAFL has usually no symptoms and in most patients, it is diagnosed as an incidental finding by abdominal ultra-sound, every third of these patients develops NASH (non-alcoholic steatohepatitis), resulting in an individual progression of the sequence of fibrosis - cirrhosis - hepatocellular carcinoma. Due to the fact, that NASH is, along with the cardiovascular causes, involved in liver-related mortality of patients with the metabolic syndrome, from clinical view, it is fundamental to distinguish between benign NAFL and potentially progressive NASH. This appears even more serious realizing that patients with NASH are being often underdiagnosed because of limited indications of liver biopsy, a common diagnostically gold standard. This work emphasizes the relationship between metabolic syndrome and liver disease and presents the main diagnostic possibilities of NAFL/NASH, the most dealing with serum markers. It is based on a research, using the PubMed database and putting the key words as search terms. Considering the huge number of patients diagnosed with fatty liver, a non-invasive, widely approachable method should be established, to make the diagnostic and staging of progression of NASH broadly possible. A new method using LCMS (Liquid Chromatography-Mass Spectrometry) analysis of serum lipids now fulfils these criteria, having high enough specificity and sensitivity, and have also been validated by comparing with a large cohort of patients diagnosed with liver biopsy.

Coping with stress: A pilot study of a self-help stress management intervention for patients with epileptic or psychogenic nonepileptic seizures.

PURPOSE: Many patients with epilepsy or psychogenic nonepileptic seizures (PNES) experience high levels of stress. Although psychological interventions have been developed for seizure disorders, few patients can currently access them. We aimed to assess the acceptability and feasibility of a self-help intervention targeting stress in patients with seizures, and to provide preliminary evidence for its effectiveness. METHOD: Patients were recruited from outpatient neurology clinics and randomized to an immediate intervention group (n = 39), who received the intervention at baseline, or a delayed intervention group (n = 43), who received the intervention one-month postbaseline. Participants completed self-report questionnaires measuring stress (Smith Stress Symptom Inventory [SSSI]), anxiety (Generalized Anxiety Disorder 7-item Scale [GAD-7]), depression (Neurological Disorders Depression Inventory for Epilepsy [NDDI-E]), quality of life (European Quality of Life - 5 Dimensions [EQ-5D]), and seizure severity and frequency (Liverpool Seizure Severity Scale [LSSS-3]) at baseline, and at one- and two-month follow-up. Participants also provided telephone feedback. The intervention consisted of a self-help stress management workbook based on an integrative stress model framework. RESULTS: Although the rate of participants failing to return follow-up information at two months was approximately 50%, those who completed the trial found the intervention acceptable; with the majority rating it as helpful (63.6%) and that they would recommend it to others with seizures (88.1%). A significant reduction in self-reported stress (P = .01) with a medium effect size (dz = 0.51) was observed one-month postintervention. There were no significant changes in any other measures. CONCLUSION: The intervention was perceived to be acceptable, safe, and helpful by participants. It could be a useful complementary treatment option for reducing stress experienced by patients living with seizure disorders. Further evaluation in a larger trial is warranted.

Early Seizure Detection Based on Cardiac Autonomic Regulation Dynamics.

Epilepsy is a neurological disorder that causes changes in the autonomic nervous system. Heart rate variability (HRV) reflects the regulation of cardiac activity and autonomic nervous system tone. The early detection of epileptic seizures could foster the use of new treatment approaches. This study presents a new methodology for the prediction of epileptic seizures using HRV signals. Eigendecomposition of HRV parameter covariance matrices was used to create an input for a support vector machine (SVM)-based classifier. We analyzed clinical data from 12 patients (9 female; 3 male; age 34.5 ± 7.5 years), involving 34 seizures and a total of 55.2 h of interictal electrocardiogram (ECG) recordings. Data from 123.6 h of ECG recordings from healthy subjects were used to test false positive rate per hour (FP/h) in a completely independent data set. Our methodological approach allowed the detection of impending seizures from 5 min to just before the onset of a clinical/electrical seizure with a sensitivity of 94.1%. The FP rate was 0.49 h-1 in the recordings from patients with epilepsy and 0.19 h-1 in the recordings from healthy subjects. Our results suggest that it is feasible to use the dynamics of HRV parameters for the early detection and, potentially, the prediction of epileptic seizures.

Diurnal patterns and relationships between physiological and self-reported stress in patients with epilepsy and psychogenic non-epileptic seizures.

PURPOSE: Patients with epilepsy and those with psychogenic non-epileptic seizures (PNES) experience high levels of stress and stress is one of the most frequently self-identified seizure precipitants. Although stress is a multifaceted phenomenon, few studies have systematically examined its different components in patients with seizures. The aim of this study was therefore to describe diurnal patterns of psychological and physiological measures of stress in patients with epilepsy and patients with PNES, and explore their relationships to each other in order to improve our understanding of the mechanisms underlying stress and seizure occurrence in these patients. METHOD: A range of stress markers including self-reported stress, salivary cortisol, and heart rate variability (HRV) were explored in adult patients with refractory epilepsy (N=22) and those with PNES (N=23) undergoing three- to five-day video-telemetry. RESULTS: A diurnal pattern was observed in the physiological measures, characterized by higher levels of physiological arousal in the mornings and lower levels at night in both patients with epilepsy and PNES. The physiological measures (cortisol and HRV) were associated with each other in patients with epilepsy; no close relationship was found with self-reported stress in either of the two patient groups. CONCLUSION: The findings contribute to and expand on previous studies of the patterns of stress in patients with seizures. The results also indicate a discrepancy between patients' physiological responses and their subjective stress perceptions, suggesting that simple self-reports cannot be used as a proxy of physiological arousal in patients with seizures and stress. Stress in these patient groups should be studied using a combination of complementary measures.

Emotion processing and psychogenic non-epileptic seizures: A cross-sectional comparison of patients and healthy controls.

PURPOSE: This exploratory study aimed to examine emotion-processing styles in patients with psychogenic non-epileptic seizures (PNES), compared to healthy individuals, and to explore associations of emotion processing with other psychological measures and seizure frequency, using the new Emotional Processing Scale (EPS-25), which had not previously been used in this patient group. METHODS: Fifty consecutive patients with PNES referred for psychotherapy completed a set of self-report questionnaires, including the Emotional Processing Scale (EPS-25), Clinical Outcome in Routine Evaluation (CORE-10), Short Form-36 (SF-36), Patient Health Questionnaire (PHQ-15), and Brief Illness Perception Questionnaire (BIPQ). Responses on the EPS-25 were compared to data from 224 healthy controls. RESULTS: Patients with PNES had greater emotion processing deficits across all dimensions of the EPS-25 than healthy individuals (suppression/unprocessed emotion/unregulated emotion/avoidance/impoverished emotional experience). Impaired emotion processing was highly correlated with psychological distress, more frequent and severe somatic symptoms, and a more threatening understanding of the symptoms. Emotion processing problems were also associated with reduced health-related quality of life on the mental health (but not the physical health) component of the SF-36. The unregulated emotions sub-scale of the EPS was associated with lower seizure frequency. CONCLUSION: The results showed clear impairments of emotion processing in patients with PNES compared to healthy individuals, which were associated with greater psychological distress and reduced mental health functioning. These findings seem to support the face validity of the EPS-25 as a measure for PNES patients and its potential as a tool to assess the effectiveness of psychological interventions.

A prospective service evaluation of acceptance and commitment therapy for patients with refractory epilepsy.

OBJECTIVE: The aims of this service evaluation were to explore the effectiveness of a psychotherapeutic treatment for patients with epilepsy based on the acceptance and commitment therapy (ACT) approach and to assess whether this treatment is likely to be cost-effective. METHOD: We conducted an uncontrolled prospective study of consecutive patients with refractory epilepsy referred for outpatient psychological treatment to a single psychotherapist because of emotional difficulties related to their seizure disorder. Participants were referred by consultant neurologists, neuropsychologists, or epilepsy nurses, completed a set of validated self-report questionnaires (Short Form - 12 version 2, Generalized Anxiety Disorder - 7, Neurological Disorders Depression Inventory for Epilepsy, Work and Social Adjustment Scale, and Rosenberg Self-Esteem Scale), and reported their seizure frequency at referral, the end of therapy, and six months posttherapy. Patients received a maximum of 20 sessions of one-to-one psychological treatment supported by a workbook. Cost-effectiveness was estimated based on the calculation of quality-adjusted life year (QALY) gains associated with the intervention. RESULTS: Sixty patients completed the prepsychotherapy and postpsychotherapy questionnaires, among whom 41 also provided six-month follow-up data. Patients received six to 20 sessions of psychotherapy (mean=11.5, S.D.=9.6). Psychotherapy was associated with significant medium to large positive effects on depression, anxiety, quality of life, self-esteem, and work and social adjustment (ps<.001), which were sustained six months after therapy. The mean cost of the psychotherapy was £445.6, and, assuming that benefits were maintained for at least six months after the end of therapy, the cost per QALY was estimated to be £11,140 (€14,119, $18,016; the cost per QALY would be half this amount if the benefits lasted one year). CONCLUSION: The findings of this pilot study indicate that the described psychotherapeutic intervention may be a cost-effective treatment for patients with epilepsy. The results suggest that a randomized controlled trial of the psychotherapy program is justified.

The role of stress as a trigger for epileptic seizures: a narrative review of evidence from human and animal studies.

Stress is one of the most frequently self-identified seizure triggers in patients with epilepsy; however, most previous publications on stress and epilepsy have focused on the role of stress in the initial development of epilepsy. This narrative review explores the causal role of stress in triggering seizures in patients with existing epilepsy. Findings from human studies of psychological stress, as well as of physiologic stress responses in humans and animals, and evidence from nonpharmacologic interventions for epilepsy are considered. The evidence from human studies for stress as a trigger of epileptic seizures is inconclusive. Although retrospective self-report studies show that stress is the most common patient-perceived seizure precipitant, prospective studies have yielded mixed results and studies of life events suggest that stressful experiences only trigger seizures in certain individuals. There is limited evidence suggesting that autonomic arousal can precede seizures. Interventions designed to improve coping with stress reduce seizures in some individuals. Studies of physiologic stress using animal epilepsy models provide more convincing evidence. Exposure to exogenous and endogenous stress mediators has been found to increase epileptic activity in the brain and trigger overt seizures, especially after repeated exposure. In conclusion, stress is likely to exacerbate the susceptibility to epileptic seizures in a subgroup of individuals with epilepsy and may play a role in triggering "spontaneous" seizures. However, there is currently no strong evidence for a close link between stress and seizures in the majority of people with epilepsy, although animal research suggests that such links are likely. Further research is needed into the relationship between stress and seizures and into interventions designed to reduce perceived stress and improve quality of life with epilepsy.